The present invention relates to novel rhodanine derivatives, processes for preparing the same and a pharmaceutical composition containing the same as a therapeutic agent for diabetic complications.
In recent years, westernization of eating habits has resulted in a marked increase in the number of diabetic patients and measures for the treatment thereof are urgently needed.
As therapeutic agents for diabetes, insulin and blood sugar lowering agents have so far been used widely. However, diabetes is not a mere disorder of sugar metabolism but a disease also involving a variety of complications and therefore the therapeutic effects of the above-mentioned agents alone are not enough for the treatment of diabetes.
Among main complications, cerebral and coronary vascular disturbances account for about 50% of causes of deaths resulting from diabetes [Y. Goto et al., Sogo Rinsho, 22, 779 to 785 (1973)].
Blood platelets play an important role in the development of such vascular disturbances. Thus, in a diabetic condition, platelets are in the state of hyperfunction, causing thrombosis and at the same time arteriosclerosis [H. Heath et al., Diabetologia, 7, 308 to 315 (1971)]. Therefore, platelet aggregation inhibitors are useful in the treatment of vascular disturbances such as mentioned above.
On the other hand, diseases of the eye, such as retinopathy and cataract, are also important diabetic complications and form the primary cause of blindness of the aged. In the development of such diseases, not only disturbance of retinal and other blood vessels, namely microangiopathy, is an important pathogenic factor, but also a certain kind of sugar metabolism disorder is concerned [K. H. Gabbay, Adv. Metab. Disord., 2(2), 424 (1973)]. Thus, in the diabetic condition, polyols such as sorbitol are accumulated to an extraordinary extent, causing osmotic pressure increase and water retention, which lead to ocular tissue disturbance. Therefore, inhibition of aldose reductase which is essential to polyol synthesis can possibly be effective in the prevention and treatment of the above-mentioned diseases of the eye [R. G. Judzewitsch et al., New Eng. J. Med., 308, 119 to 125 (1983); J. H. Kinoshita et al., Metabolism, 28 (1), 462 to 469 (1979)].